γ-Synuclein Expression Is a Malignant Index in Oral Squamous Cell Carcinoma

Abstract

Dysregulation of γ-synuclein (SNCG) has been reported in many cancers; however, its role in cancer development is still controversial. Here, we examined the potential involvement of DNA methylation in regulating SNCG and its role in oral squamous cell carcinoma (OSCC). We used 8 OSCC cell lines to investigate SNCG methylation and expression. SNCG methylation was examination by methylation-specific polymerase chain reaction and bisulfate sequencing. Cells showing a high degree of SNCG methylation were treated with 5-aza (methylation inhibitor), and changes in their methylation and expression profiles were analyzed. Functional effects of SNCG in OSCC were examined by its overexpression and knockdown. Additionally, methylation and expression of SNCG in OSCC tissues were investigated and correlated with clinicopathologic features. All OSCC cells showed detectable SNCG expression at the mRNA and protein levels. Methylation-specific polymerase chain reaction and bisulfate sequencing revealed high SNCG expression in SCC25 cells with the unmethylated allele, and their 15 CpG islands were unmethylated. The methylated allele was detected only in OEC-M1 cells exhibiting low SNCG expression, and their CpG islands were partially methylated. 5-aza treatment in OEC-M1 cells attenuated methylation and restored SNCG expression. SNCG overexpression increased colony forming, migration, and invasion abilities in OEC-M1 cells. Silencing SNCG in SCC25 cells suppressed these behaviors. All 25 tumor-adjacent normal tissues were negative for SNCG immunostaining. SNCG upregulation was frequently observed in dysplastic and OSCC tissues. Positive SNCG expression was found in 45% (37 of 82) OSCC tissues. Positive SNCG expression in OSCC significantly correlated with cancer staging and lymph node metastasis. However, SNCG methylation did not correlate with its expression and clinicopathologic variables in OSCC tissues. DNA methylation may participate in regulating SNCG expression in some OSCC cells. SNCG upregulation could be involved in OSCC progression.